一种提高流产组织染色体拷贝数检测精度和范围的新型技术及应用

A novel technology to improve the detection accuracy and range of CNVs in aborted tissues and its application

目的 基于二代测序平台,本研究开发了一种新型染色体异常检测技术—CNV-plus,旨在探究该技术的检测性能及优势,为临床中拷贝数的高精度和全面检测提供新方法。方法 使用CNV-plus对共173例流产组织样本进行染色体拷贝数检测,并通过CNV-seq和STR两种方法的验证和补充,对比分析检测结果的可检出变异类型、检测一致性及检测精度。结果 CNV-plus技术与CNV-seq对CNV有100%的检测一致性,且检测精度更高,排除母源污染后,CNV-plus与STR对三倍体有100%的检测一致性。与CNV-seq和STR相比,CNV-plus还可检出纯合性片段(ROH)变异。此外,我们将CNV-plus应用于173例流产组织的染色体异常检测结果进行统计和分析,进一步探究了不同变异类型与年龄、孕周及流产次数之间的关系。结论 CNV-plus在实现更高精度的CNV-seq检测需求的基础上,增加了对ROH和三倍体的检测,这为临床上多种变异类型的全面检测提供了准确和可靠的理论依据。同时,探究不同变异类型与自然流产间的关系可为临床上不同异常类型胎儿的诊断和咨询提供一定的参考。

Objective Based on the technology of next-generation sequencing,we developed a novel chromosomal abnormality testing method called CNV-plus.This research aimed to explore the method's detection performance and advantages,and to provide a new method for high-precision and comprehensive detection of copy number variations in clinical practice.Methods CNV-plus was used to perform chromosomal copy number variations(CNVs)detection on a total of 173 samples of spontaneous abortion.The results were validated and supplemented by CNV-seq and STR to compare and analyze the detected variation types,consistency,and accuracy.Results CNV-plus showed 100%consistency with CNV-seq in detecting CNV,with higher detection accuracy.After excluding maternal contamination,CNV-plus exhibited 10o%consistency with STR in detecting triploidy.Compared with CNV-seq and STR,CNV-plus was able to detect extra variation that was regions of homozygosity(ROH).Furthermore,we conducted statistical analysis on the chromosomal abnormality detection results of 173 samples of spontaneous abortion(SA)using CNV-plus,exploring the relationship between different types of variations and age,gestational weeks,and number of miscarriages.Conclusion CNV-plus,while achieving higher accuracy in CNV-seq detection,has added the capability to detect ROH and triploidy,providing an accurate and reliable theoretical basis for comprehensive examination of various types of copy number variations in clinical settings.Moreover,the investigation of the relationship between different abnormalities and SA,supports a valuable insight for the clinically diagnosis and counseling of fetuses with different types of CNVs.